Process for preparing synthetic absorbable poly(esteramides)

ABSTRACT

A body absorbable polymeric material for implantation which is a condensation product of reacting a diamine with lactic or glycolic acid to form a diamidediol which is then reacted with a bischloroformate or a compound selected from the group consisting of dicarboxylic acids, methyl and ethyl esters of dicarboxylic acids, diacidchlorides, and anhydrides of a dicarboxylic acid.

This is a division of application Ser. No. 103,915 filed Dec. 17, 1979,now U.S. Pat. No. 4,343,931.

This invention relates to new and useful bioabsorbable polymericmaterials derived from reacting diamidediols with a dicarboxylic acid ora bischloroformate and to the methods for the preparation of suchpolymeric materials.

It has become common practice in human and animal surgery to utilizevarious augmentation devices to restore living tissues or repair variousorgans. These surgical augmentation devices are usually placed inposition either temporarily or permanently. One such augmentation deviceis a surgical suture.

Surgical sutures were originally fabricated from naturally occurringsubstances. Such naturally occurring materials include silk and catgutor collagen. Although these naturally occurring materials are still inwidespread use, modern synthetic fibers made of nylons, polyesters,polyolefins and the like are steadily displacing the use of thesenatural materials for a variety of reasons. For example, syntheticfibers generally cause far less adverse tissue reactions and are lesslikely to potentiate infection than either silk or catgut.

In the case of the surgical suture which is placed for temporarypurposes, the suture should be made so that it is absorbed by the bodyafter serving its function in the augmentation or wound repair process.Absorbed is used herein to mean that a substantial portion of thepolymer is metabolized by the body and ultimately eliminated therefrom.

Several absorbable sutures are presently known to the art. For example,see U.S. Pat. Nos. 3,636,956 and 3,839,297. The sutures disclosed in theaforementioned patents consist of an extrusion of a polylactide polymerwhich includes a copolymer of L(-)lactide with up to 35 mole percent ofglycolide. While multifilament sutures manufactured from polymers oflactide and glycolide fulfill the requirements of a suture to a largedegree, monofilament sutures of these materials are considerably lessflexible than catgut and these synthetic sutures are accordinglygenerally limited to a multifilament, braided construction. Braidedsutures have the disadvantages of causing trauma upon being pulledthrough tissue due to a sawing action, a.k.a. tissue drag. Sutures ofglycolide polymers are also not suitable for sterilization by radiationwithout suffering severe degradation of physical properties.

Another serious disadvantage of the polyglycolide sutures is the factthat strength loss in vivo proceeds at a rapid rate. Such fibers areknown to possess virtually no strength at three to four weeks. Whilethis is not a problem in some applications, the polyglycolide suturesare contraindicated where extended approximation is advisable.

The present invention provides synthetic absorbable sutures having ahigh degree of softness and flexibility while at the same time allowingthe sutures to be used in monofilament form. The sutures can also besterilized with gamma radiation (e.g., radiation from cobalt 60) withoutserious loss of suture strength. It is accordingly an object of thepresent invention to provide synthetic absorbable sutures having uniqueand desirable properties not available with the sutures of the priorart.

The synthetic absorbable sutures of the present invention are preparedfrom a polymeric material having a plurality of units of the generalformula: ##STR1## wherein R¹ is hydrogen or methyl;

R³ and R⁵ may be identical or different and are selected from the groupconsisting of the following which may be linear or branched alkylene,alkylene having 1 or 2 nonadjacent catenary oxygen or sulfur atoms,alkenylene; cycloalkylene and arylene; and having up to 25 carbon atomsin the cyclic compounds and from 2 to 25 carbon atoms in the non-cyclic;

R² and R⁴ are hydrogen or alkyl having 1 to 4 carbon atoms or R² and R⁴together are linear or branched alkylene having one to four carbonsforming with N--R³ --N a heterocyclic group having 5 or 6 ring atoms;and

a and b are independently zero or one.

The polymeric materials of the present invention may be prepared byutilizing a process which involves reacting a diamine with lactic orglycolic acid to form a diamidediol. The resulting diamidediol is thenreacted with a dicarboxylic acid or derivative (e.g. diacidchloridediester or anhydrides) or a bischloroformate to form the polymericmaterial which can then be processed to the desired configuration.

The body absorbable surgical materials of the present invention arecomprised of a polymer of the general formula: ##STR2## in which R¹ ishydrogen or methyl;

R³ and R⁵ may be identical or different and are selected from the groupconsisting of the following, which may be linear or branched, alkylene,alkylene having 1 or 2 nonadjacent catenary oxygen or sulfur atoms,alkenylene, cycloalkylene and arylene; having up to 25 carbon atoms inthe cyclic compounds and from 2 to 25 carbon atoms in the non-cycliccompounds;

R² and R⁴ are hydrogen or alkyl having 1 to 4 carbon atoms or R² and R⁴together are linear or branched alkylene having one to four carbonsforming with N--R³ --N a heterocyclic group having 5 or 6 ring atoms;

a and b are independently zero or one; and

n having an average value from about 10 to about 100.

In order to obtain the regular sequence shown, it is desirable to firstform the amide linkages prior to polymerization. This can beaccomplished by combining about two moles of glycolic or lactic acidwith about one mole of a diamine and heating at a temperature between150° to 220° C. until distillation of water is complete. Alternatively,combination of hydroxy acid and diamine will produce a salt which can bepurified by recrystallization and then subjected to the abovecondensation. In either case, a high yield of diamidediol is obtainedwhich can be purified by recrystallization.

Diamidediols useful in synthesizing polymers of this invention can beprepared by the above methods from diamines such as 1,2-ethanediamine;1,3-propanediamine; 1,3-(2-methylpropane)diamine;1,3-(2,2-dimethylpropane)diamine; 1,2-(1,2-dimethylethane)diamine;1,4-butanediamine; 1,5-pentanediamine; 1,6-hexanediamine;1,7-heptanediamine; 1,8-octanediamine; 1,9-nonanediamine;1,10-decanediamine; 1,11-undecanediamine; 1,12-dodecanediamine;1,13-tridecanediamine; 1,14-tetradecanediamine; 1,15-pentadecanediamine;1,16-hexadecanediamine; 3-oxapentane-1,5-diamine;4-oxaheptane-1,7-diamine; 5-oxanonane-1,9-diamine;6-oxaundecane-1,11-diamine; 7-oxatridecane-1,13-diamine;8-oxapentadecane-1,15-diamine; 9-oxaheptadecane-1,17-diamine;10-oxanonadecane-1,19-diamine; 11-oxaheneicosane-1,21-diamine;12-oxatricosane-1,23-diamine; 13-oxapentacosane-1,25-diamine;4,9-dioxadodecane-1,12-diamine; 3,6-dioxaoctane-1,8-diamine and otheranalogs of oxa-aliphatic diamines and the corresponding thia-aliphaticdiamines; cyclohexane-1,4-diamine; cyclohexane-1,3-diamine;cyclohexane-1,2-diamine; 1,4-bis(aminomethyl)cyclohexane;1,3-bis(aminomethyl)cyclohexane; 1,4-bis(2-aminoethyl) cyclohexane;1,4-bis(3-aminopropyl)cyclohexane; bis(4-aminocyclohexyl)methane;p-phenylenediamine; o-phenylenediamine; m-phenylenediamine;p-xylylene-α,α-diamine and other aromatic diamines; piperazine;4,4'-trimethylenedipiperidine; 4,4'-bipiperidine;N,N'-bis(3-aminopropyl)piperazine; 2,5-dimethylpiperazine;2,6-dimethylpiperazine; 2-methylpiperazine; imidazolidine;2-methylimidazolidine; 4,5-dimethylimidazolidine.

In the preferred body absorbable polymeric material, it is preferredthat the diamidediols be a mixture of1,12-di(hydroxyacetamido)-4,9-dioxadodecane and1,12-di(hydroxyacetamido)dodecane, with groups R¹, R², R³, and R⁴ beingformed by the removal of the elements of water in the condensation ofglycolic acid with 4,-9,-dioxa-1,12-dodecane diamine and1,12-dodecanediamine.

Synthesis of the body absorbable polymer of the present invention can beaccomplished by any of a number of well known techniques. For example,the diamidediol can be combined with an equimolar amount of one or moredicarboxylic acids or dicarboxylic acid methyl esters and appropriateesterification catalyst, e.g. Sb₂ O₃, and heated with stirring undernitrogen at temperatures of 150° to 250° C. for 10 to 100 hours with175° to 200° C. for 20 to 40 hours being preferred.

A preferred method of preparing polymer consists of dissolving thediamidediol in a solvent which is nonreactive with acid chlorides andhas a boiling point of 100° C. or higher, heating the mixture to reflux,and rapidly adding an equimolar amount of a diacid chloride withvigorous mechanical mixing (e.g. motor driven paddle), separating thepolymer from solvent and drying the polymer at temperatures below themelting point of the polymer. Suitable solvents includemethylchloroacetate, chlorobenzene 1,1,2-trichloroethane or1,4,-dioxane. The preferred solvent for uses with a diacid chloride ischlorobenzene.

The preferred method has the advantages of not requiring catalyst, ofyielding product in a relatively short period of time, and producinghigh molecular weight polymer in a granular, easy-to-manipulate form. Inaddition, moisture which would otherwise react with the acid chloridecan be readily excluded from the system by azeotropic distillation priorto addition of the diacid chloride. Polymer prepared by this method canbe further improved with respect to increasing the molecular weight byheating for several days under partial vacuum with a stream of drynitrogen passing over the polymer at temperatures that are 10° to 50° C.below the polymer melting temperature.

Dicarboxylic acid chlorides and the diacid dimethyl or diethyl esters ofdicarboxylic acids useful in the synthesis of polymers by the abovemethods include those derived from the dicarboxylic acids listed below.In addition, the free acids can also be used. The term "dicarboxylicacid" as used herein includes dicarboxylic acids, their methyl and ethylesters, their acid chlorides and hydrides. They are, for example, oxalicacid; malonic acid; succinic acid; 2,3-dimethylsuccinic acid; glutaricacid; 3,3-dimethylglutaric acid; 3-methyladipic acid; adipic acid;pimelic acid; suberic acid; azelaic acid; sebacic acid;1,9-nonanedicarboxylic acid; 1,10-decanedicarboxylic acid;1,11-undecanedicarboxylic acid; 1,12-dodecanedicarboxylic acid;1,13-tridecanedicarboxylic acid; 1,14-tetradecanedicarboxylic acid;1,15-pentadecanedicarboxylic acid; 1,16-hexadecanedicarboxylic acid;maleic acid; trans-β-hydromuconic acid; fumaric acid; diglycolic acid;3,3'-oxydipropionic acid; 4,4'-oxydibutyric acid; 5,5'-oxydivalericacid; 6,6'-oxydicaproic acid; 8,8'-oxydicaprylic acid;6-oxaundecanedioic acid; 5-oxaazelaic acid; 5-oxasebacic acid;5-oxaundecanedioic acid; 5-oxadodecanedioic acid; 5-oxatetradecanedioicacid; 5-oxahexadecanedioic acid; 6-oxadodecanedioic acid;6-oxatridecanedioic acid; 6-oxapentadecanedioic acid;6-oxaheptadecanedioic acid; 7-oxapentadecanedioic acid;10-oxanonadecanedioic acid and other oxa-aliphatic dicarboxylic acids;phthalic acid; isophthalic acid; tetrephthalic acid and other aromaticdicarboxylic acids; 1,2-cyclobutanedicarboxylic acid;1,4-cyclohexanedicarboxylic acid. In the preferred body absorbablepolymeric material, R⁵ is preferrably ethylene being formed by theremoval of the chloride from succinyl chloride.

Polymers can also be prepared by reaction of the diamidediols withbischloroformates. The bischloroformates, in turn, can be prepared byreacting a dihydroxy compound with excess phosgene gas in the condensedphase or in solution (see Preparative Methods of Polymer Chemistry, 2nded., Sorenson and Campbell, Interscience Pub (1968), p.123). Dihydroxycompounds that can be used include, for example, the previouslymentioned diamidediols; ethylene glycol; 1,3-propanediol;1,4-butanediol; 1,5-pentanediol; 1,6-hexanediol; 1,7-heptanediol;1,8-octanediol; 1,9-nonanediol; 1,10-decanediol; 1,11-undecanediol;1,12-dodecanediol; 1,13-tridecanediol; 1,14-tetradecanediol;1,15-pentadecanediol; 1,16-hexadecanediol; oxaaliphatic diols andpoly(ethyleneoxy)diols of various molecular weights.

The polymeric materials of this invention can be fabricated into filmsand fibers by melt extrusion. When the films are fabricated into fibers,it is preferred that n of the general formula have an average value fromabout 30 to about 50. Such fibers have been implanted subcutaneously inmice and have been found to be non-irritating and compatible with theliving tissue over the time span of many months. After approximatelyeight months, a substantial amount of the polymer is absorbed by theliving tissue.

The polymers of the present invention are also useful in the manufactureof cast and/or extruded films and molded solid surgical aids. Thus,cylindrical pins, screws, reinforcing plates, etc., may be machined fromthe cast or molded polymer having the aforementioned in vivo absorptioncharacteristics.

The preparation of the body absorbable polymeric material of the presentinvention may be further illustrated by reference to the followingexamples:

EXAMPLE 1 1. Synthesis of 1,12-di(hydroxyacetamido)dodecane

Two moles of vacuum redistilled 1,12-dodecanediamine (400 g) weredissolved in 5 liters of isopropyl alcohol in a 6 liter stainless steelbeaker and four moles of glycolic acid (304 g) were added carefully insmall portions with stirring. The resultant solution was covered withaluminum foil and allowed to cool gradually to room temperaturewhereupon formation of a white crystalline solid occurred. The crystalswere collected on a large Buchner funnel, rinsed with isopropanol, andair dried yielding 647 g (92%), m.p. 94°-97° C.

The solid was placed in a 5 liter round bottom 3-neck flask and heatedin a large oil bath with overhead stirring. A stream of dry nitrogen waspassed into the system and through the attached distillation apparatus.The melted solid was heated to 190° C. at which temperature vigorousdistillation of water occurred. After 4 hours evolution of water hadsubsided completely and the liquid was poured into metal pans where itrapidly solidified. The product was recrystallized from 6 liter ofabsolute methanol to yield 530 g (84%) of lustrous white crystals; m.p.127°-130° C.; infrared (Nujol) 1650 cm⁻¹, 3250 cm⁻¹ ; proton nuclearmagnetic resonance (DMSO-d₆ /TMS, 100 MHz) δ1.27 (singlet, 20 protons),δ3.13 (quartet, 4 protons), δ3.82 (doublet, 4 protons), δ5.47 (triplet,2 protons), and δ7.73 (broad triplet, 2 protons).

2. Synthesis of poly[dodecane-1,12,di-(carbonyloxy)dodecane-1,12-di(amidocarbonylmethylene)]

Exactly 486.3 g (1.54 moles) of 1,12-di(hydroxyacetamido)dodecane and397.0 g (1.54 moles) of 1,12-dodecanedicarboxylic acid were meltedtogether in a 2 liter glass resin flask heated in an oil bath. Overheadstirring of the molten mixture was commenced and 0.8 g of Irganox 1010(a phenolic antioxidant available from Ciba-Giegy) added. Dry nitrogenwas admitted through a tube reaching below the surface of the liquid.The mixture was heated at 175° C. for 20 hours during which timedistillation of water occurred. Antimony trioxide (0.8 g) was added andheating and stirring were continued for an additional 16 hours at 200°C. The viscous, light brown colored product was poured out and allowedto solidify. The solid was dissolved in 15 liter of boiling isopropanoland the solution allowed to cool to 30° C. at which temperature theprecipitated solid was collected and dried to yield 525 g of powder;inherent viscosity 0.26 (0.5% in 1,1,1-trifluoroethanol (TFE) at 30°C.); differential thermal analysis, Tg=-1 to +20° C., Tm=93° C.

3. In vivo evaluation

The above polymer was melt extruded in a 3/4 inch Brabender Extruderequipped with 30:1 L/D ratio general purpose screw and oriented at atemperature above its glass transition temperature by drawing at a ratiobetween about 4 to 1 and 10 to 1 to produce uniform fiber with atenacity of 2.5 g/denier. The fiber was cut into 20 cm lengths whichwere alternately assigned to control and experimental groups. All fiberwas handled the same with respect to ethylene oxide sterilization anddrying. The experimental set of fibers were surgically implantedsubcutaneously in mice. The mice were necropsied at various timeintervals and the tensile strength of recovered fiber measured afterdrying and compared with control samples. The data recorded in Table 1was obtained by averaging 8 to 10 individual values recorded at eachtime period.

                  TABLE 1                                                         ______________________________________                                        Days Post     Tensile Strength                                                Implantation  Retained                                                        ______________________________________                                        5             46.6%                                                           7             28.0%                                                           14            12.3%                                                           ______________________________________                                    

Additional fiber implanted mice were necropsied at monthly intervals.After two months the fibers possessed virtually no physical integrity,were broken into small pieces approximately 1 to 2 mm in length, andwere encapsulated. By six months only a trace of the polymer could bedetected visually, the majority having been completely absorbed. In allof these evaluations there was no visible reaction to the surroundingtissue and no evidence of toxicity.

EXAMPLE 2 Alternate sythesis ofpoly[dodecane-1,12-di(carbonyloxy)dodecane-1,12-di(amidocarbonylmethylene)

Dimethyl-1,12-dodecanedicarboxylate (19.72 g, 0.069 mole) and1,12-di(hydroxyacetamido)dodecane (21.79 g, 0.069 mole) preparedaccording to the procedure in Example 1 were placed in a 250 ml roundbottom 3-neck flask and heated in an oil bath with overhead stirring.About 10 mg of Irganox 1010, and zinc acetate (about 10 mg) were addedand the mixture heated to 185° C. with dry nitrogen passing over thereactants and through the attached distillation apparatus. Heating andstirring were continued for 20 hours at 170°-185° C. Antimony trioxide(about 10 mg) was added and the temperature maintained at 190°-200° C.for an additional 20 hours. During this time the melt increased inviscosity and high vacuum was applied intermittently. The dark brownproduct was allowed to cool and was then dissolved in hot isopropylalcohol (1 liter). The isopropyl alcohol solution was allowed to cool to30° C. at which temperature the precipitated solid was collected anddried to yield 30.1 g of powder; inherent viscosity 0.27 (0.5% in TFE at30° C.); differential thermal analysis, Tg=+3 to +24° C., Tm=117° C.

The powdered polymer was placed in a glass U tube and heated in an oilbath for 60 hours at 97° C. During this time a slow stream of drynitrogen was passed through the polymer which remained in the solidstate. As a result of this treatment the inherent viscosity increasedsignificantly (0.36). Filaments pulled from the melted polymer wereeasily cold drawn by hand to yield tenacious fibers.

EXAMPLE 3 1. Synthesis of poly[oxysebacoyloxydodecane1,12-di(amidocarbonylmethylene)]

Exactly 404.7 g (1.28 moles) of 1,12-di(hydroxyacetamido)dodecaneprepared according to the procedure in Example 1 and 258.5 g (1.28moles) of sebacic acid were melted together in a 2 liter glass resinflask heated in an oil bath. Overhead stirring was commenced and 0.6 gof Irganox 1010 antioxidant added. Dry nitrogen was admitted through atube reaching below the surface of the liquid. The mixture was heated at175° C. for 20 hours during which time distillation of water occurred.0.6 g of antimony trioxide was added and heating and stirring continuedfor an additional 20 hours at 190° C. Nitrogen flow was discontinued,the system was placed under vacuum of about 0.1 Torr, and heating andstirring continued for 4 hours at 210° C. The reaction was thendiscontinued and the viscous, brown liquid poured into a metal pan whereit solidified into a hard, tough solid. The solid was dissolved in 3liters of boiling isopropanol and the solution poured slowly into 4liters of acetone with vigorous stirring. The resultant precipitate wascollected and dried to yield 430 g of powder; inherent viscosity 0.32(0.5% in TFE at 30° C.); differential analysis, Tg=-10 to +9, Tm=50° C.

2. In vivo evaluation

The above polymer was melt extruded and oriented as in Example 1 toproduce uniform fiber with a tenacity of 0.82 g/denier. The fiber wasimplanted in mice as described in Example 1. The strength loss resultsare shown in Table 2.

                  TABLE 2                                                         ______________________________________                                        Days Post     Tensile Strength                                                Implantation  Retained                                                        ______________________________________                                        3             61.4%                                                           10            18.8%                                                           ______________________________________                                    

The implantation site in each of the mice showed no visible inflammationor other evidence of an adverse reaction toward the polymer.

EXAMPLE 4 1. Synthesis of 1,10-di(hydroxyacetamido)decane

1,10-Decanediamine (10 g, 0.058 mole) was dissolved in 150 ml of boilingisopropanol and solid glycolic acid (8.8 g, 0.116 mole) addedportion-wise with stirring. An oil that separated from the cooledsolution rapidly crystallized upon scratching. Recrystallization fromisopropanol yielded white crystals (16.3 g, 87% yield, m.p. 57°-62° C.).

The 1,10-decanediammonium glycolate was placed in a 3-neck 100 ml roundbottom flask and heated in an oil bath with magnetic stirring. Drynitrogen was passed over the melted solid and through the attacheddistillation apparatus. Distillation of water occurred at 150° C. After4 hours at 150°-165° C., no further evolution of water could be detectedand the liquid was poured into a dish where it rapidly solidified.Recrystallization from methanol gave 10.7 g (74%) of white crystals;m.p. 120°-122° C.

2. Synthesis ofpoly[decane-1,10-di(carbonyloxy)decane-1,10-di(amidocarbonylmethylene)]

Exactly 9.50 g (0.033 mole) of 1,10-di(hydroxyacetamido)decane and 7.66g (0.033 mole) of 1,10-decanedicarboxylic acid were placed in a 100 mlround bottom flask and heated in an oil bath with overhead stirring.Irganox 1010 antioxidant (about 5 mg) was added and the mixture heatedto 170° C. with dry nitrogen passing over the reactants and through theattached distillation apparatus. Heating and stirring were continuedovernight (16 hours) at 170° C. Antimony trioxide (about 5 mg) was addedand the temperature increased to 190°-210° C. for 8 hours. During thistime the melt became rather viscous and a vacuum of about 0.1 Torr wasapplied intermittently. The melt was allowed to cool completelyovernight and was then reheated to 210° C. for 2 hours followed by anadditional 30 minutes under vacuum. The viscous, amber colored productwas poured onto a metal surface where it cooled to form a tough solid;inherent viscosity 0.26 (0.5% in TFE at 30° C.); differential thermalanalysis, Tg=-8 to +2° C., Tm=51° C. Filaments pulled from the meltedpolymer were easily cold drawn by hand to yield tenacious fibers.

EXAMPLE 5 1. Synthesis of poly[oxysuccinoyloxydodecane1,12-di(amidocarbonylmethylene)]

Exactly 390.4 g (1.235 moles) of 1,12-di(hydroxyacetamido)dodecaneprepared according to the procedure in Example 1 and 1 kg ofchlorobenzene were placed in a 3 liter resin flask and heated in an oilbath with overhead stirring. The solid dissolved and approximately 200ml of chlorobenzene was distilled from the solution. The solution wasallowed to cool to 120° C. and the distillation apparatus was replacedwith a reflux condenser connected to gas washing bottles, the firstempty and the second filled with water. Vacuum redistilled succinylchloride (191.5 g, 1.235 moles) was added cautiously through an additionfunnel to the solution while stirring at approximately 300 rpm. Theexothermic reaction was accompanied by vigorous evolution of hydrogenchloride gas. Approximately 20 minutes after addition of succinylchloride, the solution became viscous and the polymer solidified andseparated from the solution. The mixture was refluxed with stirring foran additional 2 hours during which time the evolution of hydrogenchloride subsided. The chlorobenzene was removed by distillation underreduced pressure to yield 490 g of product; inherent viscosity 0.45(0.5% in TFE at 30 ° C.); differential thermal analysis, Tg=+16 to +48°C., Tm=160° C.

The product was placed in a 3-neck flask and heated in an oil bath for48 hours at 130° C. During this time a slow stream of dry nitrogen waspassed through the polymer which remained in the solid state. As aresult of this treatment the inherent viscosity increased significantly(0.81).

2. In vivo evaluation

The above polymer was melt extruded and oriented as in Example 1 toproduce uniform fiber corresponding to U.S.P. suture size number 00 witha tenacity of 2.4 g/denier. Two commercial U.S.P. number 00 absorbablesutures, Vicryl (Ethicon, Inc.) and chromic catgut (Ethicon, Inc.), werepurchased and included in the evaluation. The in vivo fiber strengthretention data was obtained as described in Example 1 and is shown inthe accompanying figure.

The strength loss profile of fiber produced in this example illustratesthat this polymer should be useful clinically where approximation ofhealing tissue is required for a longer period of time than canpresently be achieved with currently available absorbable sutures.

The implantation site revealed no evidence of irritation orincompatibility in each of the necropsies involving the above polymer.This was not the case with chromic catgut, however, which producedinflammatory reactions varying from slight to massive.

EXAMPLE 6 1. Synthesis of 4,4'-methylenebis(hydroxyacetamidocyclohexane)

4,4'-Methylenebis(cyclohexylamine) (56.5 g, 0.27 mole) was dissolved inhot isopropanol (500 ml) and glycolic acid (40.9 g, 0.54 mole) addedportion-wise with stirring. Upon cooling, a white gummy solid separatedwhich was isolated by decantation and redissolved in a small volume ofethanol. Crystallization produced a white crystalline, deliquescentsolid; m.p. 96°-102° C. Thorough drying under vacuum increased themelting point (m.p. 149°-151° C.) and reduced the deliquescence.

The solid was placed in a 250 ml round bottom flask and heated in an oilbath with stirring. Distillation of water occurred at 150° C. and thetemperature was increased to 175° C. After stirring at 175° C. for 3hours the melt suddenly resolidified into a white crystalline mass. Thesolid was recrystallized from a mixture of ethanol and methanol to yieldlustrous, white crystals, m.p. 208°-211° C.; infrared (Nujol), 1630cm⁻¹, 3250 cm⁻¹ ; proton nuclear magnetic resonance (CDCl₃ /TMS, 100MHz), δ0.6-1.5 (complex multiplet, 12 protons), δ1.5-1.8 (doublet, 8protons , δ3.50 (broad singlet, 2 protons), δ3.75 (doublet, 4 protons),δ5.35 (triplet, 2 protons), δ7.37 (doublet, 2 protons).

2. Alternate synthesis of 4,4'-methylenebis(hydroxyacetamidocyclohexane)

4,4'-Methylenebis(cyclohexylamine) (25 g, 0.12 mole) and glycolic acid(18.2 g, 0.24 mole) were combined in a 250 ml round bottom flask heatedin an oil bath. The solids were melted together with mixing and heatedto 175° C. whereupon distillation of water occurred. After heating for 3hours the evolution of water subsided and crystallization commenced. Thesolid was removed and recrystallized from methanol to yield 34 g (87%)of lustrous white needles; m.p. 208°-212° C.

3. Synthesis ofpoly[decane-1,10-di(carbonyloxy)dicyclohexylmethane-4,4'-di(amidocarbonylmethylene)]

Exactly 1.748 g (0.0065 mole) of 1,10-decanedicarbonyl chloride wasplaced in a 100 ml round bottom flask and dissolved in chlorobenzene (20ml). 4,4'-Methylenebis(hydroxyacetamidocyclohexane) (2.120 g, 0.0065mole) was added and the mixture heated to reflux with stirring. Vigorousevolution of hydrogen chloride occurred, and after refluxing forapproximately 30 minutes the mixture became a clear, colorless solution.

Refluxing was continued for 2 hours and the solution then allowed tocool whereupon precipitation occurred. The precipitate was collected byfiltration and dried under vacuum to give a white powder; inherentviscosity (0.5% in TFE at 30° C.) of 0.35; differential thermalanalysis, Tg=+75° to +85° C., Tm=185° C. Filaments pulled from themelted polymer were easily cold drawn by hand to give tenacious fibers.

EXAMPLE 7 Synthesis of poly[ethane-1,2,-di(oxycarbonyloxy)dicyclohexylmethane-4,4'-di(amidocarbonylmethylene)]

Exactly 5.643 g (0.0301 mole) of vacuum redistilled ethylenebischloroformate were placed in a 50 ml round bottom flask and 20 ml ofchlorobenzene added followed by 9.837 g (0.0301 mole) of4,4'-methylenebis(hydroxyacetamidocyclohexane) prepared according to theprocedure in Example 6. The mixture was heated in an oil bath to 130° C.with rapid magnetic stirring. Vigorous evolution of hydrogen chloridegas occurred and the mixture turned dark yellow in color. Afterrefluxing the mixture for 2 hours, the solid was collected by filtrationand dried under vacuum to yield a light tan colored powder; inherentviscosity 0.09 (0.5% in TFE at 30° C.); infrared (Nujol), 1650 cm⁻¹,1750 cm⁻¹ ; differential thermal analysis, Tg=+70 to +84° C., Tm=180° C.with decomposition.

EXAMPLE 8 1. Synthesis oftrans-1,4-cyclohexanebis(hydroxyacetamidomethyl)

Glycolic acid (313 g, 4.12 moles) was dissolved in 2 liter of absolutemethanol and a methanolic solution of 1,4-cyclohexanebis(methylamine)(291 g, 2.05 moles, approximately 20% cis and 80% trans isomers) addedcarefully with stirring. The hot solution was boiled for 3 to 5 minutesand then cooled slowly to 4° C. whereupon crystallization occurred. Thewhite, crystalline product was collected on a Buchner funnel, rinsedwith methanol, and dried under vacuum at 60° C. to yield 541 g (89.5%);m.p. 199°-201° C.

The glycolic acid salt was placed in a 3 liter 3-neck round bottom flaskheated in an oil bath with mechanical stirring. Dry nitrogen was passedinto the system and through the attached distillation apparatus. Uponheating to 210° C., vigorous distillation of water occurred and subsidedcompletely after 45 minutes. 73.8 g (99.5%) of water were collected. Thesolidified product was dissolved in 6 liters of hot absolute ethanol andallowed to cool slowly to room temperature whereupon crystallizationoccurred. The clusters of long, pale yellow colored needles which formedwere collected and dried to yield 273 g (51.4%); m.p. 182°-186° C.;infrared (Nujol), 1625 cm⁻¹, 3270 cm⁻¹ ; proton nuclear magneticresonance (DMSO-d₆ /TMS, 100 MHz), δ0.6-1.9 (complex multiplet, 10protons), δ2.98 (triplet, 4 protons), δ3.83 (doublet, 4 protons), δ5.44(triplet, 2 protons), δ7.67 (triplet, 2 protons).

The filtrate was concentrated to a volume of 2 liters and cooled to -20°C. whereupon a powdery white solid appeared. The solid was collected anddried to yield 104 g (19.6%); m.p. 136°-142° C. The proton nuclearmagnetic resonance spectrum for this material is essentially the same asabove except that the multiplet at δ3.0 is more complex and themultiplet at δ0.6-1.9 is partially replaced by a singlet occurring atδ1.35. It is estimated that this lower melting fraction is approximately40% trans and 60% cis isomers of the desired product whereas the highermelting major fraction is virtually pure trans isomer. It is believedthat fractional crystallization is possible due to the fact that the cisisomer can form intramolecular hydrogen bonds whereas the trans isomercannot.

2. Synthesis of poly[trans-oxysebacoyloxycyclohexane-1,4-di(methyleneamidocarbonylmethylene)]

186.0 g (0.721 mole) of trans-1,4-cyclohexanebis(hydroxyacetamidomethyl)were placed in a 3 liter 3-neck round bottom flask and 800 g ofchlorobenzene added. The mixture was heated with overhead stirring andapproximately 150 ml of chlorobenzene distilled from the solution. Thedistillation apparatus was then replaced with a reflux condenser as inExample 5. Vacuum redistilled sebacoyl chloride (172.3 g, 0.721 mole)was added carefully through an addition funnel with rapid stirring.Vigorous evolution of hydrogen chloride gas occurred and the productseparated as a granular solid. The mixture was refluxed for 2 hoursduring which time evolution of hydrogen chloride gas subsided.Filtration while hot and drying under vacuum yielded 208 g of powder;inherent viscosity 0.60 (0.5% in TFE at 30° C.); differential thermalanalysis, Tg=+50 to +57° C., Tm=180° C.

The polymer was melt extruded and oriented as in Example 1 to produceuniform fiber with a tenacity of 1.70 g/dienier.

EXAMPLE 9 1. Synthesis of N,N'-di(hydroxyacetyl)piperazine

Piperazine hexahydrate (17.5 g, 0.090 mole) was dissolved in 1 liter ofabsolute methanol and solid glycolic acid (13.7 g, 0.180 mole) addedwith stirring. The solution was boiled for a few minutes and thenallowed to cool slowly. Crystallization produced long, white needleswhich were collected and dried under vacuum to give 16.3 g (76%); m.p.169°-173° C. The product was placed in a 100 ml round bottom flask andheated in an oil bath with magnetic stirring. A stream of dry nitrogenwas passed through the system and the temperature maintained at180°-190° C. for 3 hours. After distillation of water subsided, theliquid was solidified and recrystallized from 1 liter of absoluteethanol to give a white powder; m.p. 187°-190° C.; infrared (Nujol),1625 cm⁻¹, 3250 cm⁻¹ ; proton nuclear magnetic resonance (DMSO-d₆ /TMS,100 MHz), δ3.43 (singlet, 8 protons), δ4.12 (singlet, 4 protons), δ4.63(broad singlet, 2 protons).

2. Synthesis of poly(oxysuccinoyloxy)piperazineN,N'-di(carbonylmethylene)

N,N'-di(hydroxyacetyl)piperazine (2.70 g, 0.0133 mole) was placed in a50 ml round bottom flask and 15 ml of chlorobenzene added. The mixturewas stirred magnetically and vacuum redistilled succinyl chloride (2.07g, 0.0133 mole) added. The mixture was heated in an oil bath at120°-130° C. for 3 hours during which time evolution of hydrogenchloride gas occurred. The product was collected by filtration and driedunder vacuum to yield a tan colored powder; inherent viscosity 0.14(0.5% in TFE at 30° C.); differential thermal analysis, Tg=+55 to +75°C., Tm=200° C. with decomposition.

EXAMPLE 10 1. Synthesis of 1,12-di(hydroxyacetamido)-4,9-dioxadodecane

4,9-Dioxadodecane-1,12-diamine (22.8 g, 0.112 mole) was placed in a 250ml round bottom flask and glycolic acid (17.0 g, 0.224 mole) addedportion-wise with stirring and cooling. The resultant liquid was heatedin an oil bath to 185° C. whereupon distillation of water occurred.Heating was continued at 185° to 195° C. for 2 hours after which timedistillation of water subsided and the liquid was poured into acrystallization dish. The resultant oil slowly crystallized in the formof large white clusters; yield 35.5 g (99.3%); m.p. 67°-71° C. The solidwas recrystallized from cold absolute methanol to give a white,crystalline product; m.p. 74°-77° C.; infrared (Nujol), 1120 cm⁻¹, 1625cm⁻¹, 3250 cm⁻¹ ; proton nuclear magnetic resonance (CDCl₃ /TMS, 100MHz), δ1.55-1.95 (complex multiplet, 8 protons), δ3.30-3.65 (complexmultiplet, 12 protons), δ4.03 (singlet, 4 protons), δ4.98 (broadsinglet, 2 protons), δ7.51 (broad triplet, 2 protons).

2. Synthesis ofpoly[oxysuccinoyloxy-4,9-dioxadodecane-1,12-di(amidocarbonylmethylene)]

Redistilled succinyl chloride (5.437 g, 0.035 mole) was placed in a 100ml round bottom flask and diluted with chlorobenzene (40 ml). Thesolution was stirred magnetically and1,12-di(hydroxyacetamido)-4,9-dioxadodecane (11.224 g, 0.035 mole)added. The mixture was heated in an oil bath to 50° C. whereuponevolution of hydrogen choride gas commenced and an oily layer separated.The mixture was refluxed for 2 hours and then allowed to cool. Thesolidified product was collected and dried under vacuum at 50° C. togive a waxy material; inherent viscosity 0.16 (0.5% in TFE at 30° C.);differential thermal analysis, Tg=-11° to -4° C., Tm=72° C.

EXAMPLE 11 1. Synthesis ofpoly[oxysuccinoyloxydodecane-1,12-di(amidocarbonylmethylene)-co-10%-oxysuccinoyloxy-4,9-dioxadodecane-1,12-di(amidocarbonylmethylene)]

Exactly 457.8 g (1.449 moles) of 1,12-di(hydroxyacetamido)dodecaneprepared according to the procedure in Example 1 and 51.5 g (0.161 mole)of 1,12-di(hydroxyacetamido)-4,9-dioxadodecane prepared according to theprocedure in Example 10 were placed in a 5 liter resin flask and 1.5 kgof chlorobenzene added. The reaction was conducted as described inExample 5. After distillation of approximately 200 ml of chlorobenzene,249.5 g (1.610 moles) of redistilled succinyl chloride was added throughan addition funnel to the rapidly stirring solution. Approximately 20minutes after addition of succinyl chloride, the solution became viscousand the polymer soon solidified and separated from the solution. Themixture was refluxed with stirring for an additional 2 hours duringwhich time the evolution of hydrogen chloride subsided. The product wascollected by filtration and dried under vacuum at 100° C. to yield 524 gof powder; inherent viscosity 0.31 (0.5% in TFE at 30° C.); differentialthermal analysis, Tg=+16 to +38° C., Tm=135° C.

The product was placed in a dish and heated in a vacuum oven for 6 daysat 128° C. under partial vacuum. During this time a slow stream of drynitrogen was passed over the polymer which remained in the solid state.As a result of this treatment the inherent viscosity increasedsignificantly (0.48).

2. Fiber evaluation

The above polymer was melt extruded and oriented as described in Example1 to produce uniform fiber with a tenacity of 1.93 g/denier, 43%elongation, and modulus of 1.37. This fiber is noticeably more flexiblethan the fiber prepared from homopolymer in Example 5.

EXAMPLE 12 Synthesis of poly[3-oxapentane-1,5-di(carbonyloxy)dodecane-1,12-di(amidocarbonylmethylene)]

Anhydrous dioxane (250 ml) and 1,12-di(hydroxyacetamido)dodecane (46.9g, 0.148 mole) prepared according to the procedure in Example 1 wereplaced in a 500 ml round bottom flask and heated under reflux withoverhead mechanical stirring. Redistilled diglycoyl chloride (25.4 g,0.148 mole) was added cautiously through an addition funnel to therefluxing solution. The hydrogen chloride gas which evolved wasentrained in a stream of dry nitrogen and trapped in a water filled gaswashing bottle. An oily layer soon separated from the solution andrefluxing was continued for 4 hours. The mixture was then allowed tocool and the solidified material collected and dried under vacuum togive 67.4 g of product; inherent viscosity 0.23 (0.5% in TFE at 30° C.);differential thermal analysis, Tg=+19° to +53° C., Tm=124° C.

The polymer was placed in a U shaped tube and heated in an oil bath at100° to 115° C. for 5 days. During this time a slow stream of drynitrogen was passed through the polymer which remained in the solidstate. As a result of this treatment the inherent viscosity increasedsignificantly (0.34). Filaments pulled from the melted polymer wereeasily cold drawn by hand to give tenacious fiber.

EXAMPLE 13 1. Synthesis of 4,4'-methylenebis(α-hydroxypropiamidocyclohexane)

Molten 4,4'-methylenebis(cyclohexylamine) (224.0 g, 1.065 moles) wasplaced in a 1 liter round bottom flask and 85% lactic acid (225.5 g,2.13 moles) added slowly through an addition funnel with stirring andcooling. The resultant liquid was then heated in an oil bath to 190° C.whereupon distillation of water occurred. Heating was continued at 190°C. for 4 hours after which time distillation of water subsided and theliquid was poured into a Pyrex baking dish. Upon cooling the productsolidified into a clear, amber colored glass. The solid was broken upand recrystallized twice from tetrahydrofuran containing 10% methanol togive lustrous, white flakes; m.p. 195°-199° C.; infrared (Nujol), 1640cm⁻¹, 3300 cm⁻¹ ; proton nuclear magnetic resonance (DMSO-d₆ /TMS, 100MHz), δ0.6-1.5 (complex multiplet with doublet superimposed at δ1.15, 18protons), δ1.5-1.8 (doublet, 8 protons), δ3.50 (broad singlet, 2protons), δ3.7-4.1 (multiplet, 2 protons), δ5.35 (doublet, 2 protons),δ7.30 (doublet, 2 protons).

2. Synthesis ofpoly[oxysebacoyloxycyclohexane-1,4-di(amidocarbonylethyledene)]

Exactly 86.0 g (0.2427 mole) of 4,4'-methylenebis(hydroxypropiamidocyclohexane) were placed in a 1 liter 3-neck roundbottom flask and 600 ml of chlorobenzene added. The mixture was heatedwith overhead stirring and approximately 50 ml of chlorobenzenedistilled. The solid remained undissolved and formed a thick suspension.Vacuum redistilled sebacoyl chloride (58.0 g, 0.2427 mole) was addedcarefully through an addition funnel with rapid stirring. This causedthe diamidediol to dissolve and form a clear, colorless solution. Theheating and stirring were continued for 45 min. during which time HClevolved and the solution viscosity increased markedly The solvent wasthen removed by distillation under reduced pressure and the resultingsolid product kept under high vacuum overnight at 115° C. Upon cooling,the flask broke in numerous places. This polymer gave no adhesivefailure with the glass flask which had to be removed by pulverization.The polymer is a hard, tough, colorless, thermoplastic solid which canbe cold drawn to give strong, rigid filaments; inherent viscosity 1.17(0.5% in TFE at 30° C.); differential thermal analysis, Tg=+90 to 100°C., Tm=199° C.

EXAMPLE 14 1. Synthesis ofpoly[oxysuccinoyloxydodecane-1,12-di(amidocarbonylmethylene)-co-10%-oxysuccinoyoxy-4,9-dioxadecane-1,12-di-(amidocarbonylmethylene)]

A ten gallon glass-lined reaction kettle equipped with a refluxcondenser, pyrometer, addition funnel, and dry nitrogen purge wascharged with exactly 1,942.4 g (6.15 moles) of1,12-di(hydroxyacetamido)dodecane prepared according to the procedure inExample 1, 218.6 g (0.68 moles) of1,12-di(hydroxyacetamido)-4,9-dioxadodecane prepared according to theprocedure in Example 10, and 6 gallons of chlorobenzene. The reactionkettle was heated by means of a steam jacket to 130° C. for 30 minuteswith stirring to insure complete dissolution of the diamidediolmonomers. The temperature was then stabilized at 125° C. and thestirring speed increased to the maximum setting. Exactly 1,058.6 g (6.83moles) of vacuum redistilled succinyl chloride was added through theaddition funnel at a constant rate during the time course of 3 minutesand 40 seconds. Stirring and heating were continued at 125° C. for 30minutes after which time the stirring rate was decreased and the reactorallowed to cool to room temperature. The granular product was collectedon a large ceramic filter, rinsed with heptane, and placed in a vacuumoven at 100° C. After drying for 2 days the inherent viscosity was 0.92(0.5% in TFE at 30° C.) and increased to 1.03 after heating in the ovenunder partial vacuum and a slow stream of dry nitrogen for an additional4 days at 120° C.

2. Fiber evaluation

The above polymer was melt extruded and oriented as described in Example1 to produce 2-0 suture size fiber with a tenacity of 6.53 g/denier,34.8% elongation, and modulus of 20.6 g/denier. The number of throws forthe interlacement of the parts to hold a surgeon's knot is two, theminimum possible number, and the knot strength is 47.5% of the tensilestrength.

EXAMPLE 15 1. Synthesis ofpoly[oxysuccinoyloxydodicane-1,12-di(amidocarbonylmethylene)-co-10%-3-oxapentane-1,5-di(carbonyloxy)dodecane-1,12-di(amidocarbonylmethylene)]

A five gallon glass-lined reaction kettle equipped with a refluxcondenser, pyrometer, addition funnel, and dry nitrogen purge wascharged with exactly 1,165 g (3.67 moles) of1,12-di(hydroxyacetamido)dodecane prepared according to the procedure inExample 1, and 3 gallons of chlorobenzene. The reaction kettle washeated by means of a steam jacket to 130° C. for 30 minutes withstirring to insure complete dissolution of the monomer. The stirringspeed was then increased to the maximum setting and a mixture of exactly63.3 g (0.37 moles) of vacuum redistilled diglycoyl chloride and 511.5 g(3.30 moles) of vacuum redistilled succinyl chloride added through theaddition funnel during the time course of 6 minutes and 45 seconds. Thereaction mixture was stirred and refluxed for an additional 2 hoursafter which time the stirring rate was decreased and the mixture allowedto cool to room temperature. The granular product was collected on alarge ceramic filter, rinsed with tetrahydrofuran, and placed in avacuum oven at 130° C. After heating the product at 130° C. underpartial vacuum and a slow stream of dry nitrogen for 5 days, theinherent viscosity was 0.58 (0.5% in TFE at 30° C.).

2. Fiber evaluation

The above polymer was melt extruded and oriented as in Example 1 toproduce 2-0 suture size fiber with a tenacity of 4.11 g/denier, 26.8%elongation, and modulus of 20.5 g/denier. The knot strength was 58% ofthe tensile strength.

3. In vivo evaluation

The above fiber was implanted in mice as described in Example 1. Thestrength loss results are shown in Table 3 and in the accompanyingfigure.

                  TABLE 3                                                         ______________________________________                                        Days Post     Tensile Strength                                                Implantation  Retained                                                        ______________________________________                                        7             89.7%                                                           14            83.9%                                                           28            79.4%                                                           49            38.2%                                                           ______________________________________                                    

At eight months post-implantation the encapsulated fiber was broken intosmall fragments, 1 to 4 mm in length. These fragments were extremelysoft and partially absorbed. The implantation site in each of the miceshowed no visible inflammation or other evidence of an adverse reactiontoward the polymer.

EXAMPLE 16 1. Synthesis ofpoly[oxysuccinoyloxydodecane-1,12-di(amidocarbonylmethylene)-co-20%-oxysuccinoyloxy-4,9-dioxadodecane-1,12-di(amidocarbonylmethylene)]

This polymer was prepared under exactly the same conditions described inExample 14 using 1,264 g (4.00 moles) of1,12-di(hydroxyacetamido)dodecane prepared according to the procedure inExample 1, 320 g (1.00 mole) of1,12-di(hydroxyacetamido)-4,9-dioxadodecane prepared according to theprocedure in Example 10, 775 g (5.00 moles) of vacuum redistilledsuccinyl chloride, and 3.5 gallons of chlorobenzene. The succinylchloride was added during the time course of 5 minutes and 10 secondsand the product was dried for 2 days at 130° C. to give an inherentviscosity of 0.99 (0.5% in TFE at 30° C.).

2. Fiber Evaluation

The above polymer was melt extruded and oriented as in Example 1 toproduce 2-0 suture size fiber with a tenacity of 4.67 g/denier, 38.2%elongation, and modulus of 18.0 g/denier. The knot strength was 64% ofthe tensile strength.

3. In vivo evaluation

The above fiber was implanted in mice as described in Example 1. Thestrength loss results are shown in Table 4.

                  TABLE 4                                                         ______________________________________                                        Days Post     Tensile Strength                                                Implantation  Retained                                                        ______________________________________                                        7             89.2%                                                           14            87.4%                                                           28            76.6%                                                           49            57.3%                                                           ______________________________________                                    

At eight months post-implantation the encapsulated fiber was broken intosmall fragments, 1 to 2 mm in length. These fragments were extremelysoft and partially absorbed. The implantation site in each of the miceshowed no visible inflammation or other evidence of an adverse reactiontoward the polymer.

EXAMPLE 17 1. Synthesis ofpoly[oxysuccinoyloxydodecane-1,12-di(amidocarbonylmethylene)]

This polymer was prepared under the same conditions described in Example14 using 1,081.4 g (3.42 moles) of 1,12-di(hydroxyacetamido)dodecaneprepared according to the procedure in Example 1, 530.4 g (3.42 moles)of vacuum redistilled succinyl chloride, and 3 gallons of chlorobenzene.The succinyl chloride was added during the time course of 15 minutes and13 seconds and the product was dried for 7 days at 130° C. to give aninherent viscosity of 0.58 (0.5% in TFE at 30° C.).

2. Fiber evaluation

The above polymer was melt extruded and oriented as in Example 1 toproduce 2-0 suture size fiber with a tenacity of 5.03 g/denier, 31.0%elongation, and modulus of 22.0 g/denier. The knot strength was 50% ofthe tensile strength.

What is claimed is:
 1. A process for making a body absorbable polymericmaterial having a plurality of units of the general formula: ##STR3## inwhich R¹ is hydrogen or methyl;R³ and R⁵ are identical or different andare groups selected from the class consisting of linear and branchedalkylene, alkylene having 1 or 2 nonadjacent catenary oxygen or sulfuratoms, alkenylene, cycloalkylene and arylene; said groups having up to25 carbon atoms in the cyclic compounds and from 2 to 25 carbon atoms inthe non-cyclic compounds; R² and R⁴ are hydrogen or alkyl having 1 to 4carbon atoms or R² and R⁴ together are linear or branched alkylenehaving one to four carbons forming with N--R³ --N a heterocyclic grouphaving 5 or 6 ring atoms; and a and b are independently zero or onesaidprocess comprising the steps of: reacting at least one diamine withlactic or glycolic acid to form at least one diamidediol; and reactingsaid at least one diamidediol with a bischloroformate or a compoundselected from the group consisting of dicarboxylic acids, methyl andethyl esters of dicarboxylic acids, diacidchlorides, and anhydrides of adicarboxylic acid to provide said body adsorbable polymeric material. 2.The process of claim 1 wherein said diamidediol is placed in a solventprior to reacting with said compound or said bischloroformate.
 3. Theprocess of claim 1 wherein said compound is succinyl chloride.
 4. Theprocess of claim 2 wherein said solvent is selected from the groupconsisting of chlorobenzene, 1,1,2-trichloroethane and 1,4-dioxane. 5.The process of claim 2 which includes the additional step of removingsaid solvent after reacting with said compound or said bischloroformate.6. The process of claim 1 wherein said diamidediol is a mixturecomprised of 1,12-di(hydroxyacetamido)-4,9-dioxadodecane and1,12-di(hydroxyacetamide)dodecane.